The most desirable form of cancer chemotherapy is one in which the agent(s) selectivity destroys the cancer cell without harm to normal cells. One method of developing such agents is to find some exploitable difference in tumor cell metabolism. This metabolic difference need not occur uniquely in tumors; the particular pathway may function in normal cells. The normal cell, however, may have alternative means of reaching the same end product, while the tumor does not. The proposed work will deal primarily with energy production, i.e., oxidative respiration stemming from amino acid and carbohydrate intermediate metabolic pathways, and related aspects of glycolysis. Our working hypothesis says that a partial or full citric acid cycle in tumor tissues is fueled by glutamate and that controlling influences are exerted by aspartate, asparagine, and glutamine levels as well as control inter-relationships with glucolysis, e.g. Pasteur and Crabtree effects, glucose, lactate, NAD ion/NADH levels or the function of the citric acid cycle. The experiments planned include: a) the effects of amino acids on O2 uptake, CO2 production, and lactate formation in Morris hepatomas, mouse lymphoma 6C3HED, and control tissues: b) metabolism of glutamate-C14, quantitative distribution of label into C14-O2, citric acid cycle intermediates, aspartate, and lactate; c) the effects of the amino acids and oncolytic agents on the function of isolated mitochondrial fractions from tumor and control tissues.